The activity of proteases is important in epidermal homeostasis. Thus, proteases have various potential benefits when applied to the skin, but are subject to certain limitations. Papain is a powerful protease derived from papaya and certain other plants. However, it loses activity rapidly in a solution state. This is because papain, similar to all proteases, digests itself as well as undergoes denaturation. In addition, other difficulties with conventional papain products may be encountered when these papain products are used as topical skin care agents in connection with skin penetration and skin irritation. It is highly desirable to develop protease products, and more particularly, a papain product, for use in skin care which do not have such limitations.
To overcome the above-mentioned difficulties in the conventional art, exemplary embodiments of the present invention provide a modified stable crosslinked protease product via the techniques set forth described herein, and particularly a modified stable crosslinked protease product.
For example, in some embodiments of the present invention, in order to obtain a stable crosslinked papain product, papain is immobilized on a polymer like, for example, a carbomer or carbopol in a primary cross-linking reaction and then a secondary crosslinking reaction is subsequently performed by adding a homobifunctional crosslinking reagent of low molecular weight which is amine reactive such as, for example, Dimethyl adipimidate (DMA), Bis(Sulfosuccinimidyl) suberate (BS3), Dimethyl Suberimidate (DMS), Dimethyl pimelimidate (DMP) and Disuccinimidyl suberate (DSS).
In other exemplary embodiments of the present invention, the primary crosslinking reaction and the secondary crosslinking reaction are performed to obtain a stable crosslinked papain product and then the stable crosslinked papain is further stabilized using physical stabilizers such as, for example, sugars or sugar polymers. For example, sodium alginate may be used as a physical stabilizer in accordance with exemplary embodiments of the present invention.
The above crosslinked stabilized papain product may still even be further stabilized by including the above stabilized papain product in certain preservative systems or an oil in water formulation.
The benefits of the immobilized, crosslinked and stabilized protease (e.g. papain) complex according to exemplary embodiments of the present invention include but are not limited to:                1) minimal skin penetration,        2) retention of proteasic activity in solution or dry form        3) minimal skin irritation, and        4) ease of formulation        
In still other embodiments of the present invention, cosmetic, personal care, and pharmaceutical compositions comprising stabilized proteases are described.